First-in-Human Study of RGT-419B Alone and With Endocrine Therapy in Subjects With HR-Positive, HER2-Negative Advanced/Metastatic Breast Cancer

October 11, 2023 updated by: Regor Pharmaceuticals Inc.

First-in-Human, Escalating Oral Dose Study of RGT-419B Given Alone and With Endocrine Therapy in Subjects With Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Advanced/Metastatic Breast Cancer

This is a phase I, First-in-Human (FIH), open-label study to evaluate the safety, tolerability, pharmacokinetic (PK) profile, and preliminary efficacy of RGT-419B administered orally as monotherapy OR in combination with Hormonal Therapy in subjects with HR+, HER2- locally advanced and unresectable (Stage III) or metastatic (Stage IV) breast cancer whose disease has progressed during prior therapy with an approved CDK4/6i plus hormonal therapy.

Study Overview

Study Type

Interventional

Enrollment (Estimated)

18

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Florida
      • Port Saint Lucie, Florida, United States, 34952
        • Recruiting
        • Hem-Onc Associates of the Treasure Coast
        • Contact:
          • Heather Yeckes-Rodin, MD
          • Phone Number: 772-335-5666

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male or female >/= 18 years old
  2. ECOG Performance Status 0 to 1
  3. HR+, HER2- tumor by most recent biopsy with measurable disease
  4. Have had no more than 1 prior line of cytotoxic chemotherapy in the ABC setting AND no serious/severe toxicity to a prior CKD4/6i AND no known contraindication to receiving RT-419B AND have had all acute/residual toxic effects of any prior therapy
  5. In the ABC setting, eligible subjects must have failed to respond to or progressed after <3 lines of prior CDK4/6i therapy and unlimited lines of prior HT and have had no more than 1 prior line of chemotherapy. Eligible subjects must have received and progressed on any combination of HTs including any approved AI, SERD, or SERM, and/or any approved CDK4/6i in any order.

(5a) For subjects in Arm B, at least one line of prior therapy must have included a locally approved HT which was well tolerated and which the subject is willing to receive again (5b) Subjects with tumors harboring a PIK3CA mutation will be allowed to enroll, and treatment with a PI3Ki in combination with HT will be allowed as a prior line of therapy. Surgical excision of tumor tissue accompanied by chemotherapy or targeted therapy is also counted as 1 line of prior treatment.

Exclusion Criteria:

  1. Presence of visceral metastases with severe organ dysfunction as evidence by signs and symptoms, laboratory studies, lymphangitic spread and/or rapid progression of disease
  2. Pregnant or planning to become pregnant
  3. Prior irradiation to >25% of the bone marrow and/or inadequate bone marrow function or evidence of clinically significant end-organ damage
  4. Major surgery, chemotherapy, targeted therapy, experimental agents, or radiation within 14 days prior to Cycle 1, Day 1
  5. Active, serious medical condition that is not well controlled with locally approved medications allowed by the protocol
  6. History of allergic reactions attributed to compounds of similar chemical or biologic composition to the drugs used in the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A
RGT-419B given alone as monotherapy
oral capsules
Experimental: Arm B
RGT-419B in combination with Hormonal Therapy
RGT-419B in combination with hormonal therapy (Selective Estrogen Receptor Degrader, Selective Estrogen Receptor Modulator, or Aromatase Inhibitor)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety & Tolerability - Number of subjects with Dose-Limiting Toxicities (DLTs) at each cohort dose level in singlet and doublet therapy
Time Frame: 4 weeks (1 cycle)
Number of subjects who have a confirmed DLT at each cohort dose level in singlet and doublet study arms during the first 28-day cycle of RGT-419B treatment.
4 weeks (1 cycle)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety & Tolerability - Incidence, Severity, and Causality of all Treatment Emergent Adverse Events (TEAEs)
Time Frame: through study completion, an average of 1 year
Incidence, severity, and causality of all TEAEs will be assessed for all patient participating from Day 1 dosing through end of study.
through study completion, an average of 1 year
Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Cmax
Time Frame: through study completion, an average of 1 year
Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification
through study completion, an average of 1 year
Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Area Under Concentration-Time Curve (AUC0-t)
Time Frame: through study completion, an average of 1 year
Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification
through study completion, an average of 1 year
Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Area Under Concentration-Time Curve to Infinity (AUC0-inf)
Time Frame: through study completion, an average of 1 year
Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification
through study completion, an average of 1 year
Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Plasma Decay Half-Life (t 1/2)
Time Frame: through study completion, an average of 1 year
Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification
through study completion, an average of 1 year
Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame: through study completion, an average of 1 year
Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification
through study completion, an average of 1 year
Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Accumulation rate after multiple doses
Time Frame: through study completion, an average of 1 year
Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification
through study completion, an average of 1 year
Day 1 and steady-state PK assessment of RGT-419B and major metabolites - Cumulative urinary excretion
Time Frame: through study completion, an average of 1 year
Plasma and urine samples that are being collected for PK assessment may also be used for exploratory metabolite identification
through study completion, an average of 1 year
Tumor Response assessed by Investigator according to RECIST v1.1
Time Frame: through study completion, an average of 1 year
Tumor response measured by radiologic imaging techniques at baseline and throughout the study
through study completion, an average of 1 year
QTc Interval - Changes in corrected QT interval
Time Frame: through study completion, an average of 1 year
Number of subjects with a clinically significant increase from baseline in corrected QT (QTc) interval on repeated ECGs during RGT-419B monotherapy.
through study completion, an average of 1 year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Symptom Burden
Time Frame: through study completion, an average of 1 year
Change from baseline in symptom burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) from baseline to end of treatment
through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 4, 2022

Primary Completion (Estimated)

February 28, 2024

Study Completion (Estimated)

August 28, 2024

Study Registration Dates

First Submitted

February 24, 2022

First Submitted That Met QC Criteria

March 30, 2022

First Posted (Actual)

March 31, 2022

Study Record Updates

Last Update Posted (Actual)

October 13, 2023

Last Update Submitted That Met QC Criteria

October 11, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • RGT-419B_01-101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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